3hqj

Structure-function analysis of Mycobacterium tuberculosis acyl carrier protein synthase (AcpS).


The crystal structure of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) was solved at 1.95 Å. It crystallized as one monomer per asymmetric unit. Since Mtb AcpS has biologically active trimeric arrangement, AcpS trimer (in lime, blue , and orange ) was constructed using the 3-fold crystallographic symmetry in the P23 space group. The 3′,5′-ADP moieties of the coenzyme A (CoA, colored magenta ), are positioned in the cleft between each of two monomers forming three active sites within AcpS trimer. The active site is formed by the residues D9 (highly conserved), E58, L62, and S65 from monomer A and by R92, P93, R53, H116, and T115 from the neighboring monomer B. The residues labeled and shown as sticks (A and B in the brackets point on the name of the monomer). Hydrogen bonds are shown as dashed lines with interatomic distances in Å. The magnesium (Mg) atoms are shown in spacefill representation and colored in cyan. The CoA is shown in stick representation and colored magenta. Nitrogen and <font color='red'>oxygen atoms of the CoA 3′,5′-ADP moiety and of the active site resudues are colored <font color='blue'>blue and <font color='red'>red, respectively.

<scene name='3hqj/Align/2'>Structural alignment of the structures of the Mtb AcpS trimer (in <font color='lime'>lime, <font color='blue'>blue , and <font color='orange'>orange ) and the B. subtilis AcpS trimer (1f7t, in <font color='red'>red , <font color='cyan'>cyan , and <font color='yellow'>yellow ) reveals that the Mtb AcpS structure is similar to those of other members of group I phosphopantetheine transferase (PPT) family. The <scene name='3hqj/Align/3'>important difference is that the extended α3 helix of Mtb AcpS has open conformation. Such open conformation permits to the extended loop of one monomer (<font color='lime'>lime ) to interact with adjacent monomer (<font color='blue'>blue ). The considerably shorter α3 of one B. subtilis AcpS monomer (<font color='red'>red ) has closed conformation and this doesn't allow interaction with the neighboring monomer (<font color='cyan'>cyan ).

The B. subtilis AcpS trimer (1f80) <scene name='3hqj/Acp/2'>binds three molecules of the acyl carrier protein (ASP). The interactions between B. subtilis AcpS and ACP are predominantly <scene name='3hqj/Acp/3'>electrostatic. The B. subtilis AcpS (white) is shown in spacefill representation, the agrinines, lysines, and histidines are colored <font color='blue'>blue, while aspartates and glutamates are colored <font color='red'>red. The ACP molecule (<font color='lime'>lime ) is shown in ribbon representation with aspartates and glutamates as sticks and colored <font color='red'>red. The B. subtilis AcpS has large <scene name='3hqj/Acp/4'>electropositive interface with ASP. <scene name='3hqj/Acp/5'>Electrostatic representation of Mtb AcpS surface using the similar orientation as B. subtilis AcpS, shows a moderate electronegative nature in the putative ACP binding site near the <font color='red'>ASP 15. The Mtb ASPM structure (1klp, corresponding to ACP) demonstrates considerably lower negative charge. So, the electrostatic interactions between Mtb AcpS and ASPM are, probably, less important. </StructureSection>

About this Structure
3HQJ is a 1 chain structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference
Page seeded by OCA on Wed Sep 16 09:11:05 2009